Chemically modified cellulose fibrous meshes for use as tissue engineering scaffolds

Abstract

Cellulose and sulfated cellulose fibrous meshes exhibiting robust structural and mechanical integrity in water were fabricated using a combination of electrospinning, thermal-mechanical annealing and chemical modifications. The sulfated fibrous mesh exhibited higher retention capacity for human recombinant bone morphogenetic protein-2 than the cellulose mesh, and the retained proteins remained biologically active for at least 7 days. The sulfated fibrous mesh also more readily supported the attachment and osteogenic differentiation of rat bone marrow stromal cells in the absence of osteogenic growth factors. These properties combined make the sulfated cellulose fibrous mesh a promising bone tissue engineering scaffold.

What is claimed is:  
     
       1. A fibrous mesh of thermal-mechanically annealed cellulose that is subsequently oxidized and sulfated, 
       wherein the thermal-mechanical annealing is performed under a pressure in the range from about 10 MPa to about 500 MPa and at a temperature from about 60° C. to about 240° C.; and wherein
 the fibrous mesh have thicknesses from about 10 μm to about 500 μm and comprise fibers from about 100 nm to about 20 μm in fiber diameter; 
 the fibrous mesh comprises fibers having a tensile elastic modulus from 2 MPa to 20 MPa and an ultimate tensile strength from 50 KPa to 1.0 MPa. 
 
     
     
       2. A biocompatible mesh composition, comprising:
 fibrous sulfated cellulose, wherein the sulfated cellulose was obtained from thermal-mechanically annealed and subsequently chemically modified cellulose acetate; and 
 a therapeutic material absorbed on the fibrous sulfated cellulose, 
 
       wherein the thermal-mechanical annealing is performed under a pressure in the range from about 10 MPa to about 500 MPa and at a temperature from about 60° C. to about 240° C., wherein
 the biocompatible mesh have thicknesses from about 10 μm to about 500 μm and comprise fibers from about 100 nm to about 20 μm in fiber diameter; 
 the biocompatible mesh comprises fibers having a tensile elastic modulus from 2 MPa to 20 MPa and an ultimate tensile strength from 50 KPa to 1.0 MPa. 
 
     
     
       3. The biocompatible mesh composition of  claim 2 , wherein the therapeutic material comprises a growth factor. 
     
     
       4. The biocompatible mesh composition of  claim 3 , wherein the growth factor is selected from isoforms of BMP (bone morphogenetic protein), VEGF (vascular endothelial growth factor), IGF (insulin-like growth factor), TGFbeta (transforming growth factor beta), FGF (fibroblast growth factor), RANKL (Receptor activator of nuclear factor kappa-B ligand), SDF (Stromal-derived factor), or TNFalpha (tumor necrosis factor alpha). 
     
     
       5. The biocompatible mesh composition of  claim 3 , wherein the growth factor is an osteogenic growth factor. 
     
     
       6. The biocompatible mesh composition of  claim 2 , wherein the therapeutic material comprises a bone marrow stromal cell (MSC). 
     
     
       7. The biocompatible mesh composition of  claim 6 , wherein the bone marrow stromal cell is present in the range from about 1000 to about 10,000,000 cells/cm 2 . 
     
     
       8. The biocompatible mesh of  claim 2 , wherein the thermal-mechanically annealed and subsequently chemically modified cellulose acetate is obtained by:
 electrospinning cellulose acetate to form cellulose acetate mesh; 
 thermal-mechanically annealing the electrospun cellulose acetate mesh; 
 deacetylating the annealed cellulose mesh; 
 oxidizing the deacetylated cellulose mesh to obtain aldehyde reactive functionalities; and 
 reacting the oxidized cellulose mesh with an amino-sulfate to obtain sulfated cellulose meshes. 
 
     
     
       9. A water-stable biocompatible fibrous mesh, prepared by the process comprising
 electrospinning cellulose acetate to form cellulose acetate meshes; 
 thermal-mechanically annealing the electrospun cellulose acetate meshes; and 
 chemically modifying the annealed cellulose acetate meshes, 
 
       wherein the thermal-mechanical annealing is performed under a pressure in the range from about 10 MPa to about 500 MPa and at a temperature from about 60° C. to about 240° C., wherein
 the water-stable biocompatible mesh have thicknesses from about 10 μm to about 500 μm and comprise fibers from about 100 nm to about 20 μm in fiber diameter; 
 the water-stable biocompatible mesh comprises fibers having a tensile elastic modulus from 2 MPa to 20 MPa and an ultimate tensile strength from 50 KPa to 1.0 MPa. 
 
     
     
       10. The water-stable biocompatible fibrous mesh of  claim 9 , wherein chemically modifying the annealed cellulose meshes comprises:
 deacetylating the annealed cellulose meshes; 
 oxidizing the deacetylated cellulose meshes to obtain aldehyde reactive functionalities; and 
 reacting the oxidized cellulose meshes with an amino-sulfate to obtain sulfated cellulose meshes.